Introduction Several prognostic factors have been identified to predict the outcome of patients with chronic lymphocytic leukemia (CLL), but only a few studies analyzed more markers together. Patients and Methods Taking advantage of a population of 608 patients, we identified the strongest prognostic markers of survival and, subsequently, in a cohort of 212 patients we integrated data of cytogenetic lesions, IGHV mutational status, and CD38 expression in a new and easy scoring system we called the integrated CLL scoring system (ICSS). ICSS defines 3 groups of risk: (1) low risk (patients with 13q − or normal fluorescence in-situ hybridization analysis results, mutated IGHV, and CD38) (2) high risk (all 11q − or 17p − patients and/or all unmutated IGHV and CD38 + patients); and (3) intermediate risk (all remaining patients). Results Using only these 3 already available prognostic factors, we were able to properly redefine patients and better predict the clinical course of the disease. Conclusion ICSS could become a useful tool for CLL patients' management.